A systematic investigation of the influence of circadian and circannual rhythms on the effects of several toxic or carcinogenic chemicals commonly found in the workplace will be made with mice. Based on previous studies it is expected that a fixed dose at one circadian time will be lethal to 10% of the animals (LDl0) or less but at another time to 80% (LD80) or more. For the purpose of distinguishing optimal conditions for tests at single or multiple time points, one or more model synchronizers will be manipulated to determine their relative roles: 1. The role of rhythms in influencing the outcome of toxicity tests will be tested; this will be done with emphasis on both the circadian and circannual frequencies. 2. From the viewpoint of circadian-stage dependence, carcinogens will be examined under a variety of conditions compatible with the usual working day of the laboratory. Time will be varied along either the presence or absence of a hormonal millieu such as a pituitary implant or a murine virus, both of which favor the genesis of breast cancer. Rhythms in temperature and other selected variables will be explored to see if they can be used as sensitive gauges or serve as harbingers of early pathology. 3. The relative strengths of competing synchronizers that influence results or that may be used to manipulate rhythms will be considered. Animals maintained under standard light-dark schedules (LD 8:16) will be compared to those subjected to staggered schedules with or without the additional influence of ignoring circadian and circannual variation may be continued and when multiple tests are required or when a single time point will suffice. The best conditions for obtaining maximal information in the most convenient manner will be decided. Thus, reliable methods are to be developed for carrying out chronobiological analyses in the context of a regular laboratory routine and without the necessity of undesirable schedules, increased staff or other unrealistic expenses. 4. The protocols, increased staff or other laboratories in this country and abroad.